Resveratrol inhibits expression of cancer-specific pentose phosphate pathway enzyme TKTL1

Abstract

Objective: The objective of this study was to identify cancer-specific metabolic enzyme Transketolase-like 1 (TKTL1) from pentose phosphate pathway as target of resveratrol, a naturally occurring nutraceutical. Methods: Methylthiazolyldiphenyl-tetrazolium bromide assay and trypan blue assay were used for the estimation of growth and proliferation. Reactive oxygen species (ROS) was estimated using 2’-7’-Dichlorodihydrofluorescein diacetate while reduced glutathione (GSH) was estimated using commercially available kit. Promoter activity, reverse transcription polymerase chain reaction, and western blotting were used for expression analysis. Results: Resveratrol treatment in HeLa cells inhibited proliferation, promoted ROS, and reduced intracellular GSH levels. In TKTL1 promoter activity assay, we found that resveratrol treatment directly inhibited promoter activity of TKTL1. Resveratrol inhibited both mRNA and protein expression of TKTL1 in a dose-dependent manner. Conclusion: This is the first report where we show that resveratrol inhibits cancer-specific isoform TKTL1 as one of its targets to elicit its anticancer activity.